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Clinical Trial Results:
A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-04236921 IN SUBJECTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Summary
EudraCT number	2011-000420-15
Trial protocol	DE HU
Global end of trial date	26 Mar 2014

Results information
Results version number	v1
This version publication date	08 Mar 2016
First version publication date	30 Jul 2015
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

B0151006

ISRCTN number

US NCT number

NCT01405196

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Jul 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 Mar 2014

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study is to evaluate and compare the efficacy of 3 dose levels of PF-04236921 to placebo in subjects with active SLE using the SLE Responder Index (SRI).

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Dec 2011

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 13

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Hungary: 9

Country: Number of subjects enrolled

Argentina: 28

Country: Number of subjects enrolled

Chile: 1

Country: Number of subjects enrolled

Colombia: 10

Country: Number of subjects enrolled

Korea, Republic of: 1

Country: Number of subjects enrolled

Moldova, Republic of: 15

Country: Number of subjects enrolled

Peru: 4

Country: Number of subjects enrolled

Romania: 7

Country: Number of subjects enrolled

United States: 92

Worldwide total number of subjects

183

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

179

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

The study started on 8 November 2011 and completed on 26 March 2014. Subjects were enrolled from 11 countries (Argentina, Chile, Columbia, Germany, Hungary, Republic of Korea, Republic of Moldova, Peru, Poland, Romania and United states).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

PF-04236921 10 milligram (10 mg)

Arm description

Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

Arm type

Experimental

Investigational medicinal product name

PF-04236921

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mg dose of PF-04236921 subcutaneously at Week 0, Week 8 and Week 16.

PF-04236921 50 mg

Arm description

Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

Arm type

Experimental

Investigational medicinal product name

PF-04236921

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for injection

Routes of administration

Subcutaneous use

Dosage and administration details

50 mg dose of PF-04236921 subcutaneously at Week 0, Week 8 and Week 16.

PF-04236921 200 mg

Arm description

Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

Arm type

Experimental

Investigational medicinal product name

PF-04236921

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for injection

Routes of administration

Subcutaneous use

Dosage and administration details

200 mg dose of PF-04236921 subcutaneously at Week 0, Week 8 and Week 16.

Placebo

Arm description

Placebo matching to PF-04236921 administered subcutaneously in the anterolateral right and left thighs.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo administered subcutaneously in the anterolateral right and left thighs at Week 0, Week 8 and Week 16.

Number of subjects in period 1	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg	Placebo
Started	45	47	46	45
Completed	34	35	23	36
Not completed	11	12	23	9
Consent withdrawn by subject	4	6	3	6
'Study Terminated by Sponsor '	-	-	9	-
Adverse Event	2	2	-	2
Unspecified	2	2	5	-
Lost to follow-up	2	2	3	1
Subject Died	1	-	3	-

Baseline characteristics

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Reporting group title

PF-04236921 10 milligram (10 mg)

Reporting group description

Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

Reporting group title

PF-04236921 50 mg

Reporting group description

Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

Reporting group title

PF-04236921 200 mg

Reporting group description

Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

Reporting group title

Placebo

Reporting group description

Placebo matching to PF-04236921 administered subcutaneously in the anterolateral right and left thighs.

Reporting group values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg	Placebo	Total
Number of subjects	45	47	46	45	183
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	39.9 ( 11.48 )	38.3 ( 10.49 )	41.3 ( 11.29 )	42.3 ( 13.04 )	-
Gender categorical
Units: Subjects
Female	43	44	43	38	168
Male	2	3	3	7	15

End points

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Reporting group title

PF-04236921 10 milligram (10 mg)

Reporting group description

Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

Reporting group title

PF-04236921 50 mg

Reporting group description

Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

Reporting group title

PF-04236921 200 mg

Reporting group description

Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

Reporting group title

Placebo

Reporting group description

Placebo matching to PF-04236921 administered subcutaneously in the anterolateral right and left thighs.

Primary: Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24

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End point title

Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24 ^[1]

End point description

SRI components: Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI 2K),British Isles Lupus Activity Group(BILAG) 2004,Physician’s Global Assessment(PhGA).Subjects classified as responder if they did not meet definition of treatment failure and met all the following criteria: greater than or equal to (>=)4 point reduction in SLEDAI 2K score; no new BILAG A organ domain score/2 new BILAG B organ domain scores; less than (<) 0.3 point increase in PhGA score. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial drug,death,hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with study participation. SLEDAI-2K:assesses improvement in disease activity(0 to 105;higher score=higher severity). BILAG:assesses disease extent, severity (A [severe] to E [no disease]). PhGA: assesses worsening in subject’s general health status(0[none] to 3[severe]). Full Analysis Set (FAS) excluding 200-mg dose group.

End point type

Primary

End point timeframe

Week 24

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	35 ^[2]	36 ^[3]	42 ^[4]
Units: Percentage of Subjects
number (not applicable)	59.9	39.2	40.1

Notes
[2] - Here, 'N' signifies subjects who completed through the Week 24 visit for each group respectively.
[3] - Here, 'N' signifies subjects who completed through the Week 24 visit for each group respectively.
[4] - Here, 'N' signifies subjects who completed through the Week 24 visit for each group respectively.

Analysis for SRI: PF-04236921 10 mg v. Placebo

Statistical analysis description

Point estimates of the Odds ratio (ORs) as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.076 ^[5]

Method

Mixed models analysis

Parameter type

Odds ratio (OR)

Point estimate

2.23

Confidence interval

level

90%

sides

2-sided

lower limit

0.89

upper limit

5.62

Notes
[5] - P-value was displayed without adjusting for multiplicity.

Analysis for SRI: PF-04236921 50 mg v. Placebo

Statistical analysis description

Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.528 ^[6]

Method

Mixed models analysis

Parameter type

Odds ratio (OR)

Point estimate

0.96

Confidence interval

level

90%

sides

2-sided

lower limit

0.38

upper limit

2.41

Notes
[6] - P-value was displayed without adjusting for multiplicity.

Secondary: Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, and 20

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End point title

Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, and 20 ^[7]

End point description

SRI components: SLEDAI 2K, BILAG 2004, PhGA. Subjects classified as responder if they did not meet definition of treatment failure and met all the following criteria: >=4 point reduction in SLEDAI 2K score; no new BILAG A organ domain score/2 new BILAG B organ domain scores; <0.3 point increase in PhGA score. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial drug,death,hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with study participation. SLEDAI-2K:assesses improvement in disease activity(0 to 105;higher score=higher severity). BILAG:assesses disease extent, severity (A [severe] to E [no disease]). PhGA: assesses worsening in subject’s general health status(0[none] to 3[severe]). Full Analysis Set (FAS) excluding 200-mg dose group; 'n' = subjects evaluable at specified time point.

End point type

Secondary

End point timeframe

Week 4, 8, 12, 16, 20

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	45	47	45
Units: Percentage of Subjects
number (not applicable)
Week 4 (n=43, 44, 45)	12.2	7.1	4.8
Week 8 (n=43, 43, 43)	26.8	21.5	26.3
Week 12 (n=39, 41, 42)	33.7	20	36.3
Week 16 (n=36, 39, 41)	48.9	28.9	37.1
Week 20 (n=36, 39, 43)	54.7	36.8	38.3

Analysis at Week 4: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.77

Confidence interval

level

90%

sides

2-sided

lower limit

0.62

upper limit

12.4

Analysis at Week 4: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.54

Confidence interval

level

90%

sides

2-sided

lower limit

0.31

upper limit

7.71

Analysis at Week 8: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.03

Confidence interval

level

90%

sides

2-sided

lower limit

0.4

upper limit

2.67

Analysis at Week 8: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.77

Confidence interval

level

90%

sides

2-sided

lower limit

0.29

upper limit

2.05

Analysis at Week 12: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.89

Confidence interval

level

90%

sides

2-sided

lower limit

0.35

upper limit

2.24

Analysis at Week 12: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.44

Confidence interval

level

90%

sides

2-sided

lower limit

0.16

upper limit

1.16

Analysis at Week 16: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.62

Confidence interval

level

90%

sides

2-sided

lower limit

0.64

upper limit

4.09

Analysis at Week 16: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.69

Confidence interval

level

90%

sides

2-sided

lower limit

0.27

upper limit

1.77

Analysis at Week 20: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.95

Confidence interval

level

90%

sides

2-sided

lower limit

0.78

upper limit

4.84

Analysis at Week 20: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.94

Confidence interval

level

90%

sides

2-sided

lower limit

0.38

upper limit

2.32

Secondary: Percentage of Subjects Achieving Modified Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, 20, and 24

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End point title

Percentage of Subjects Achieving Modified Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, 20, and 24 ^[8]

End point description

SRI components include: modified SLEDAI 2K (SLEDAI 2K without standard parameters "Low complement" and "Leukopenia"), BILAG 2004, PhGA. Subjects classified as responder if they did not meet definition of treatment failure and met all the following criteria: >=4 point reduction in SLEDAI 2K score; no new BILAG A organ domain score or 2 new BILAG B organ domain scores; <0.3 point increase in PhGA score. Treatment failure: any new/increased use of corticosteroids, immunosuppressants/antimalarial drug, death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with study participation. Modified SLEDAI-2K: assesses improvement in disease activity (0 to 102; higher score = higher severity). BILAG: assesses disease extent, severity (A [severe] to E [no disease]). PhGA: assesses worsening in subject’s general health status (0[none] to 3[severe]). FAS excluding the subjects in the 200-mg dose group; 'n' = subjects evaluable at specified time point.

End point type

Secondary

End point timeframe

Week 4, 8, 12, 16, 20, 24

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	45	47	45
Units: Percentage of Subjects
number (not applicable)
Week 4 (n=43, 44, 45)	9.5	7	9.2
Week 8 (n=43, 43, 43)	23.8	25.7	30.2
Week 12 (n=39, 41, 42)	35.6	24.9	42.6
Week 16 (n=36, 39, 41)	50.2	34	41
Week 20 (n=36, 39, 43)	56.5	46.9	42.2
Week 24 (n=35, 36, 42)	61.2	41.4	41.6

Analysis at Week 4: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.05

Confidence interval

level

90%

sides

2-sided

lower limit

0.28

upper limit

3.88

Analysis at Week 4: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.75

Confidence interval

level

90%

sides

2-sided

lower limit

0.19

upper limit

3.01

Analysis at Week 8: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.72

Confidence interval

level

90%

sides

2-sided

lower limit

0.28

upper limit

1.85

Analysis at Week 8: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.8

Confidence interval

level

90%

sides

2-sided

lower limit

0.32

upper limit

2.02

Analysis at Week 12: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.75

Confidence interval

level

90%

sides

2-sided

lower limit

0.3

upper limit

1.83

Analysis at Week 12: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.45

Confidence interval

level

90%

sides

2-sided

lower limit

0.18

upper limit

1.13

Analysis at Week 16: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.45

Confidence interval

level

90%

sides

2-sided

lower limit

0.58

upper limit

3.6

Analysis at Week 16: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.74

Confidence interval

level

90%

sides

2-sided

lower limit

0.3

upper limit

1.84

Analysis at Week 20: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

Placebo v PF-04236921 10 milligram (10 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.78

Confidence interval

level

90%

sides

2-sided

lower limit

0.72

upper limit

4.37

Analysis at Week 20: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.21

Confidence interval

level

90%

sides

2-sided

lower limit

0.5

upper limit

2.92

Analysis at Week 24: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

Placebo v PF-04236921 10 milligram (10 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.22

Confidence interval

level

90%

sides

2-sided

lower limit

0.89

upper limit

5.55

Analysis at Week 24: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

90%

sides

2-sided

lower limit

0.4

upper limit

2.46

Secondary: Percentage of Subjects Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response at Week 4, 8, 12, 16, 20, and 24

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End point title

Percentage of Subjects Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response at Week 4, 8, 12, 16, 20, and 24 ^[9]

End point description

BICLA include: BILAG-2004, SLEDAI-2K, PhGA of disease activity. Subjects classified as responder if they did not meet definition of treatment failure and met all the following criteria: BILAG-2004 improvement(all A scores at baseline improved to B/C/D, all B scores improved to C or D); no worsening in disease activity(no new BILAG-2004 A scores or =<1 new B score); no worsening of total SLEDAI-2K score; no <10 percent [%] worsening in analogue PhGA. Treatment failure: any new/increased use of corticosteroids, immunosuppressants/antimalarial, death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with study participation. BILAG:assesses disease extent, severity (A[severe] to E[no disease]). SLEDAI-2K:assesses improvement in disease activity (0 to 105; higher score=higher severity). PhGA: assesses worsening in subject’s general health status(0[none] to 3[severe]). FAS excluding 200-mg dose group; 'n' = subjects evaluable at specified time point.

End point type

Secondary

End point timeframe

Week 4, 8, 12, 16, 20, 24

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	45	47	45
Units: Percentage of Subjects
number (not applicable)
Week 4 (n=43, 44, 45)	26.2	21.7	21
Week 8 (n=43, 43, 43)	26.2	29	30.6
Week 12 (n=39, 41, 42)	33.6	39.6	33.3
Week 16 (n=36, 39, 41)	45.5	39.2	26.2
Week 20 (n=35, 39, 43)	43.7	31.6	21.7
Week 24 (n=35, 36, 42)	49.7	40.5	25.1

Analysis at Week 4: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.34

Confidence interval

level

90%

sides

2-sided

lower limit

0.53

upper limit

3.35

Analysis at Week 4: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.04

Confidence interval

level

90%

sides

2-sided

lower limit

0.41

upper limit

2.65

Analysis at Week 8: PF-04236921 10 mg v. Placebo

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.81

Confidence interval

level

90%

sides

2-sided

lower limit

0.33

upper limit

1.96

Analysis at Week 8: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.93

Confidence interval

level

90%

sides

2-sided

lower limit

0.39

upper limit

2.23

Analysis at Week 12: PF-04236921 10 mg v. Placebo

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.01

Confidence interval

level

90%

sides

2-sided

lower limit

0.42

upper limit

2.45

Analysis at Week 12: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.31

Confidence interval

level

90%

sides

2-sided

lower limit

0.55

upper limit

3.1

Analysis at Week 16: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.36

Confidence interval

level

90%

sides

2-sided

lower limit

0.95

upper limit

5.88

Analysis at Week 16: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.82

Confidence interval

level

90%

sides

2-sided

lower limit

0.74

upper limit

4.46

Analysis at Week 20: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

Placebo v PF-04236921 10 milligram (10 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.8

Confidence interval

level

90%

sides

2-sided

lower limit

1.1

upper limit

7.12

Analysis at Week 20: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.67

Confidence interval

level

90%

sides

2-sided

lower limit

0.66

upper limit

4.21

Analysis at Week 24: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.95

Confidence interval

level

90%

sides

2-sided

lower limit

1.18

upper limit

7.41

Analysis at Week 24: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.03

Confidence interval

level

90%

sides

2-sided

lower limit

0.82

upper limit

5.06

Secondary: Percentage of Subjects Achieving Pre-defined Criteria for Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Components at Week 24

Top of page

End point title

Percentage of Subjects Achieving Pre-defined Criteria for Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Components at Week 24 ^[10]

End point description

SRI components: SLEDAI 2K, BILAG 2004, PhGA. Subjects classified as responder if they did not meet definition of treatment failure, met all the following criteria: >=4 point reduction in SLEDAI 2K score; no new BILAG A organ domain score/2 new BILAG B organ domain scores;<0.3 point increase in PhGA score. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial drug,death, hospitalization/treatment discontinuation due to SLE,any flare of lupus interfering with study participation. SLEDAI-2K:assesses improvement in disease activity(0 to 105;higher score=higher severity).BILAG:assesses disease extent, severity (A[severe] to E[no disease]). PhGA: assesses worsening in subject’s general health (0[none] to 3[severe]). FAS excluding 200-mg dose group; 'n' = subjects evaluable for specified categories. Model percent estimates reported only for 'Reduction in SLEDAI Score', 'No Worsening in PhGA' categories; for remaining categories, raw percentages reported.

End point type

Secondary

End point timeframe

Week 24

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	34 ^[11]	36 ^[12]	41 ^[13]
Units: Percentage of Subjects
number (not applicable)
4 or More Points Reduction in SLEDAI Score	60.7	44.9	49.3
No New 1A/2B BILAG	100	100	90.2
No Worsening in PhGA	97.4	97.5	93.1
Treatment Failure	0	2.8	4.9

Notes
[11] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
[12] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
[13] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.

SLEDAI component: PF-04236921 10 mg v. Placebo

Statistical analysis description

>=4 points reduction in SLEDAI score: Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.205 ^[14]

Method

Mixed models analysis

Parameter type

Odds ratio (OR)

Point estimate

1.59

Confidence interval

level

90%

sides

2-sided

lower limit

0.63

upper limit

4.02

Notes
[14] - P-value was displayed without adjusting for multiplicity.

SLEDAI Component: PF-04236921 50 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.625 ^[15]

Method

Mixed models analysis

Parameter type

Odds ratio (OR)

Point estimate

0.84

Confidence interval

level

90%

sides

2-sided

lower limit

0.34

upper limit

2.08

Notes
[15] - P-value was displayed without adjusting for multiplicity.

PhGA Component: PF-04236921 10 mg v. Placebo

Statistical analysis description

No worsening in PhGA: Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.198 ^[16]

Method

Mixed models analysis

Parameter type

Odds ratio (OR)

Point estimate

2.81

Confidence interval

level

90%

sides

2-sided

lower limit

0.38

upper limit

20.65

Notes
[16] - P-value was displayed without adjusting for multiplicity.

PhGA Component: PF-04236921 10 mg v. Placebo

Statistical analysis description

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.192 ^[17]

Method

Mixed models analysis

Parameter type

Odds ratio (OR)

Point estimate

2.88

Confidence interval

level

90%

sides

2-sided

lower limit

0.39

upper limit

21.3

Notes
[17] - P-value was displayed without adjusting for multiplicity.

Secondary: Number of Subjects With Clinically Significant Laboratory Tests Results

Top of page

End point title

Number of Subjects With Clinically Significant Laboratory Tests Results

End point description

Pre-defined criteria were established for each laboratory test to define values that would be identified as of potential clinical importance. Laboratory values included Alanine Aminotransferase(ALT) [>5.0-10.0*Upper limit of normal range(ULN)], Albumin[<26-20 gram per liter(g/L)/<20 g/L], Amylase[>2.0-5.0*ULN], Aspartate Aminotransferase (AST)[>5.0-10.0*ULN], Creatine Kinase(CK)[>5.0-10.0*ULN/ >10.0*ULN], Glucose(Hyperglycemia)[>13.9-27.8millimoles/liter(mmol/L)],Hemoglobin(HGB)[<80-65g/L/<65g/L],Lipase[>2.0-5.0*ULN], Lymphocytes(Lymph.)(Absolute[Abs])[<0.5-0.2*10^3/microliter(UL)/<0.2*10^3/UL],Platelets[<50-25*10^3/UL/<25*10^3/UL],potassium (low)[<3.0-2.5 mmol/L], Sodium(low)[<130-120 mmol/L], Total Neutrophils(TN) (Abs)[<1.0-0.5*10^3/UL/ <0.5*10^3/UL], Triglycerides[>5.7-11.4 mmol/L], White Blood Cell Count(WBC)[<2.0-1.0*10^3/UL/<1.0*10^3/UL]. Safety population: all subjects who had at least 1 dose of investigational product; 'n'= subjects evaluable for specified parameter.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg	Placebo
Number of subjects analysed	45	47	46	45
Units: Subjects
ALT (n=45, 47, 45, 45)	2	0	0	0
Albumin: <26-20 g/L (n=45, 47, 45, 45)	1	1	1	1
Albumin: <20 g/L (n=45, 47, 45, 45)	0	1	0	0
Amylase (n=45, 47, 45, 45)	1	1	1	1
AST (n=45, 47, 45, 45)	0	1	0	1
CK: >5.0 -10.0*ULN (n=45,47,45,45)	0	1	1	0
CK >10.0*ULN (n=45,47,45,45)	0	1	1	0
Glucose (Hyperglycemia) (n=45,47,45,45)	1	1	0	2
HGB: <80 - 65 g/L (n=45,47,45,45)	1	0	0	1
HGB: <65 g/L (n=45,47,45,45)	1	0	0	0
Lipase (n=45,47,45,45)	0	1	1	0
Lymph.(Abs)<0.5-0.2* 10^3/UL(n=45,47,45,45)	6	9	4	8
Lymphocytes (Abs) <0.2*10^3/UL (n=45,47,45,45)	1	0	0	0
Platelets <50 - 25*10^3/UL (n=45,47,45,45)	0	0	0	2
Platelets <25*10^3/UL (n=45,47,45,45)	0	0	0	1
Potassium (low) (n=45,47,45,45)	2	1	1	1
Sodium (low) (n=45,47,45,45)	0	0	1	0
TN (Abs)<1.0-0.5*10^3/UL (n=45,47,45,45)	4	5	3	2
TN (Abs) <0.5*10^3/UL (n=45,47,45,45)	1	1	1	0
Triglycerides (n=44,47,45,45)	0	1	0	2
WBC <2.0 - 1.0*10^3/UL (n=45,47,45,45)	4	2	2	2
WBC <1.0*10^3/UL (n=45,47,45,45)	1	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects who Discontinued due to Adverse Events

Top of page

End point title

Number of Subjects who Discontinued due to Adverse Events

End point description

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of subjects who discontinued due to AEs were reported. Safety population defined as all subjects who had at least one dose of investigational product.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg	Placebo
Number of subjects analysed	45	47	46	45
Units: Subjects	3	2	3	3

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

Top of page

End point title

Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

End point description

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with treatment-emergent AEs or SAEs (excluding infectious AEs or SAEs) were reported. AEs include both SAEs and non-SAEs.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg	Placebo
Number of subjects analysed	45	47	46	45
Units: Subjects
AEs	34	36	38	40
SAEs	4	2	7	8

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-Emergent Infectious Adverse Events (AEs) or Serious Adverse Events (SAEs)

Top of page

End point title

Number of Subjects With Treatment-Emergent Infectious Adverse Events (AEs) or Serious Adverse Events (SAEs)

End point description

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with treatment-emergent infectious AEs or SAEs were reported. AEs include both SAEs and non-SAEs. Safety population defined as all subjects who had at least one dose of investigational product.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg	Placebo
Number of subjects analysed	45	47	46	45
Units: Subjects
Infectious AEs	25	28	25	26
Infectious SAEs	2	3	4	4

No statistical analyses for this end point

Secondary: Number of Subjects With Potentially Clinically Important (PCI) Electrocardiogram (ECG) Findings

Top of page

End point title

Number of Subjects With Potentially Clinically Important (PCI) Electrocardiogram (ECG) Findings

End point description

Criteria for PCI findings in ECG were defined as: heart rate <=40 beats per minute (bpm) or >=120 bpm; PR interval >=220 millisecond (msec); QT interval >=480 msec; QRS interval >=120 msec; QT interval corrected using the Fridericia formula (QTcF) >=500msec; no sinus rhythm. Safety population defined as all subjects who had at least one dose of investigational product.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg	Placebo
Number of subjects analysed	42 ^[18]	46 ^[19]	44 ^[20]	44 ^[21]
Units: Subjects
Heart Rate <=40 beats/min or >=120 beats/min	0	0	0	0
PR Interval >=200 msec	2	1	1	2
QT Interval >=480 msec	2	0	0	0
QRS Interval >=120 msec	3	1	2	2
QTcF >=500 msec	2	0	0	0
Rhythm (Not Sinus Rhythm)	0	0	0	1

Notes
[18] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
[19] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
[20] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
[21] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.

No statistical analyses for this end point

Secondary: Number of Subjects With Potentially Clinically Important Vital Signs Findings

Top of page

End point title

Number of Subjects With Potentially Clinically Important Vital Signs Findings

End point description

Criteria for PCI findings in vital signs were defined as: sitting systolic blood pressure (Increase from baseline >=20 millimeter of mercury (mm Hg) and >=160 mm Hg or a decrease from baseline >=20 mm Hg and <=90 mm Hg) and sitting diastolic blood pressure (increase from baseline >=15 mm Hg and >=90 mm Hg or decrease from baseline >=15 mm Hg and <=60 mm Hg), pulse rate (increase from baseline >=15 beats/min and >=120 beats/min or decrease from baseline >=15 beats/min and <=50 beats /min), body temperature (increase of >=2 degree Fahrenheit (F) and temperature >=101 degree F) and weight (change of >=7% in body weight). Safety population defined as all subjects who had at least one dose of investigational product.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg	Placebo
Number of subjects analysed	45	47	46	45
Units: Subjects
Sitting Systolic Blood Pressure	8	3	3	5
Sitting Diastolic Blood Pressure	14	14	12	14
Sitting Pulse Rate	1	1	0	1
Temperature	0	0	0	0
Weight	12	23	14	14

No statistical analyses for this end point

Secondary: Number of Subjects With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (Nabs)

Top of page

End point title

Number of Subjects With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (Nabs)

End point description

Human serum samples were analyzed for the presence or absence of anti-PF-04236921 antibodies. A positive ADA sample was further tested for neutralizing antibodies using a validated assay. Safety population defined as all subjects who had at least one dose of investigational product.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg	Placebo
Number of subjects analysed	45	47	46	45
Units: Subjects
Anti-drug Antibodies	1	0	1	0
Neutralizing Antibodies	0	0	0	0

No statistical analyses for this end point

Secondary: Serum concentration of PF-04236921

Top of page

End point title

Serum concentration of PF-04236921 ^[22]

End point description

Serum PF-04236921 concentrations over time were summarized. Pharmacokinetic analysis set was the subset of subjects from safety analysis set (all subjects who received at least 1 dose of investigational product) who provided at least 1 pharmacokinetic concentration. Here, 'n' signifies number of observations (non-missing concentrations) at the specified time points for each group respectively.

End point type

Secondary

End point timeframe

Day 1, Week 2, 4, 6, 8, 12, 16, 20, 24

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Serum concentration of PF-04236921 was not planned to be reported for placebo group.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg
Number of subjects analysed	45	47	46
Units: nanogram per milliliter (ng/mL)
arithmetic mean (standard deviation)
Day 1 (n=42, 45, 43)	26.3 ( 110.8 )	31 ( 146.9 )	15.2 ( 99.8 )
Week 2 (n=37, 41, 40)	1297 ( 759.4 )	5640 ( 2274 )	22780 ( 9896 )
Week 4 (n=39, 42, 38)	991.8 ( 527.6 )	4337 ( 1495 )	17550 ( 5757.1 )
Week 6 (n=39, 40, 37)	608.4 ( 330.1 )	3396 ( 1410 )	13460 ( 5416.6 )
Week 8 (n=39, 38, 30)	463.4 ( 254.9 )	2709 ( 1317.5 )	11110 ( 5023.7 )
Week 12 (n=32, 33, 28)	1210 ( 607 )	6482 ( 2487.4 )	25240 ( 8114 )
Week 16 (n=31, 36, 23)	703.2 ( 407.4 )	3886 ( 1322.1 )	16990 ( 6203.4 )
Week 20 (n=30, 34, 17)	1452 ( 726.8 )	6978 ( 2954 )	31050 ( 11368 )
Week 24 (n=31, 34, 18)	871.9 ( 450.4 )	4417 ( 2402.4 )	20150 ( 12091 )

No statistical analyses for this end point

Secondary: Percentage of Subjects With Corticosteroid Dose Reduced by Both Greater Than or Equal to (>=) 25 Percent (%) From Baseline and Less Than or Equal to (<=) 7.5 Milligrams per day (mg/day)

Top of page

End point title

Percentage of Subjects With Corticosteroid Dose Reduced by Both Greater Than or Equal to (>=) 25 Percent (%) From Baseline and Less Than or Equal to (<=) 7.5 Milligrams per day (mg/day) ^[23]

End point description

Subjects were given supplemental corticosteroids at baseline to control disease activity. The steroid taper was based on subject’s symptoms. Subjects recorded their steroid usage on a diary card. FAS excluding subjects in 200-mg dose group; Least Observation Carried Forward(LOCF) method was used to impute missing data.

End point type

Secondary

End point timeframe

Week 12, 16, 20, 24

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	PF-04236921 200 mg
Number of subjects analysed	15 ^[24]	24 ^[25]	23 ^[26]
Units: Percentage of Subjects
number (not applicable)
Week 12	13.3	20.8	8.7
Week 16	20	25	8.7
Week 20	26.7	25	8.7
Week 24	26.7	20.8	8.7

Notes
[24] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
[25] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
[26] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.

No statistical analyses for this end point

Secondary: Percentage of Subjects With Normalized Serological Activity

Top of page

End point title

Percentage of Subjects With Normalized Serological Activity ^[27]

End point description

Serologic activity was to be assessed in the subgroup of subjects who had positive serologic activity at baseline.

End point type

Secondary

End point timeframe

Baseline up to Week 24

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	0 ^[28]	0 ^[29]	0 ^[30]
Units: Percentage of Subjects
number (not applicable)

Notes
[28] - Data was not analyzed as number of subjects with abnormal values at baseline was minimal (<=25%).
[29] - Data was not analyzed as number of subjects with abnormal values at baseline was minimal (<=25%).
[30] - Data was not analyzed as number of subjects with abnormal values at baseline was minimal (<=25%).

No statistical analyses for this end point

Secondary: Patient Global Visual Analog Scale (VAS) Scores at Baseline

Top of page

End point title

Patient Global Visual Analog Scale (VAS) Scores at Baseline ^[31]

End point description

Subjects assessed their disease activity using a 100 mm VAS. Subjects answered the following question “Considering all the ways your disease affects you, how are you feeling today?” Response was recorded by placing a mark on the scale between 0 (very well) and 100 (extremely bad). FAS excluding the subjects in the 200-mg dose group.

End point type

Secondary

End point timeframe

Baseline

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	45	47	45
Units: mm
arithmetic mean (standard error)	50.44 ( 2.865 )	47.7 ( 2.88 )	49.47 ( 3.349 )

No statistical analyses for this end point

Secondary: Change From Baseline in Patient Global Visual Analog Scale (VAS) at Week 2, 4, 6, 8, 12, 16, 20 and 24

Top of page

End point title

Change From Baseline in Patient Global Visual Analog Scale (VAS) at Week 2, 4, 6, 8, 12, 16, 20 and 24 ^[32]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	45	47	45
Units: mm
least squares mean (confidence interval 95%)
Week 2 (n=44, 47, 43)	-9.17 (-15.09 to -3.26)	-1.54 (-7.22 to 4.15)	-3.58 (-9.49 to 2.34)
Week 4 (n=45, 47, 45)	-3.24 (-9.09 to 2.62)	-4.01 (-9.69 to 1.68)	-1.24 (-7.02 to 4.55)
Week 6 (n=45, 47, 45)	-5.48 (-11.33 to 0.37)	-3.62 (-9.31 to 2.06)	-7.24 (-13.02 to -1.45)
Week 8 (n=45, 47, 45)	-4.17 (-10.02 to 1.68)	-6.03 (-11.71 to -0.34)	-7.11 (-12.89 to -1.32)
Week 12 (n=45, 47, 45)	-9.21 (-15.07 to -3.36)	-4.2 (-9.88 to 1.49)	-6.88 (-12.67 to -1.1)
Week 16 (n=45, 47, 45)	-8.75 (-14.6 to -2.89)	-10.2 (-15.88 to -4.51)	-5.99 (-11.78 to -0.21)
Week 20 (n=45, 47, 45)	-11.52 (-17.38 to -5.67)	-9.03 (-14.71 to -3.34)	-6.77 (-12.56 to -0.99)
Week 24 (n=45, 47, 45)	-9.17 (-15.02 to -3.32)	-7.45 (-13.14 to -1.77)	-10.64 (-16.42 to -4.85)

Analysis at Week 2: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

-5.41

Confidence interval

level

90%

sides

2-sided

lower limit

-12.3

upper limit

1.49

Analysis at Week 4: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

Placebo v PF-04236921 10 milligram (10 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

-1.39

Confidence interval

level

90%

sides

2-sided

lower limit

-8.21

upper limit

5.42

Analysis at Week 6: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

1.3

Confidence interval

level

90%

sides

2-sided

lower limit

-5.71

upper limit

8.32

Analysis at Week 8: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

4.67

Confidence interval

level

90%

sides

2-sided

lower limit

-2.22

upper limit

11.57

Analysis at Week 12: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

-3.98

Confidence interval

level

90%

sides

2-sided

lower limit

-11.04

upper limit

3.07

Analysis at Week 16: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

-2.89

Confidence interval

level

90%

sides

2-sided

lower limit

-9.87

upper limit

4.1

Analysis at Week 20: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

-6.21

Confidence interval

level

90%

sides

2-sided

lower limit

-13.37

upper limit

0.94

Analysis at Week 24: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

1.98

Confidence interval

level

90%

sides

2-sided

lower limit

-5.17

upper limit

9.13

Analysis at Week 2: PF-04236921 50 mg v. Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

2.07

Confidence interval

level

90%

sides

2-sided

lower limit

-4.7

upper limit

8.84

Analysis at Week 4: PF-04236921 50 mg v. Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

-2.81

Confidence interval

level

90%

sides

2-sided

lower limit

-9.62

upper limit

Analysis at Week 4: PF-04236921 50 mg v.Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

3.97

Confidence interval

level

90%

sides

2-sided

lower limit

-2.95

upper limit

10.9

Analysis at Week 8: PF-04236921 50 mg v.Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

2.56

Confidence interval

level

90%

sides

2-sided

lower limit

-4.29

upper limit

9.4

Analysis at Week 12: PF-04236921 50 mg v.Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

3.14

Confidence interval

level

90%

sides

2-sided

lower limit

-3.67

upper limit

9.94

Analysis at Week 16: PF-04236921 50 mg v.Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

-4.94

Confidence interval

level

90%

sides

2-sided

lower limit

-11.91

upper limit

2.03

Analysis at Week 20: PF-04236921 50 mg v.Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

-2.64

Confidence interval

level

90%

sides

2-sided

lower limit

-9.61

upper limit

4.32

Analysis at Week 24: PF-04236921 50 mg v.Placebo

Statistical analysis description

Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean difference

Point estimate

2.66

Confidence interval

level

90%

sides

2-sided

lower limit

-4.48

upper limit

9.8

Secondary: Change From Baseline in European Quality of Life 5 Dimensions Questionnaire (EQ-5D) at Week 4, 8, 12, 16, 20 and 24

Top of page

End point title

Change From Baseline in European Quality of Life 5 Dimensions Questionnaire (EQ-5D) at Week 4, 8, 12, 16, 20 and 24 ^[33]

End point description

EQ-5D is a standardized, subject-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point VAS (0= worst imaginable health state, 100= best imaginable health state).

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20, 24

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	0 ^[34]	0 ^[35]	0 ^[36]
Units: Units on a scale
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[34] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.
[35] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.
[36] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.

No statistical analyses for this end point

Secondary: Thirty six-Item Short-Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Baseline

Top of page

End point title

Thirty six-Item Short-Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Baseline ^[37]

End point description

SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as PCS and MCS. The score for each aspect and PCS/MCS is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). FAS excluding the subjects in the 200-mg dose group.

End point type

Secondary

End point timeframe

Baseline

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	43 ^[38]	46 ^[39]	45
Units: Units on a scale
arithmetic mean (standard error)
MCS	39.5 ( 1.81 )	42.36 ( 1.426 )	39.94 ( 1.45 )
PCS	33.47 ( 1.169 )	34.36 ( 1.25 )	34.64 ( 1.523 )

Notes
[38] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
[39] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.

No statistical analyses for this end point

Secondary: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) PCS and MCS at Week 4, 8, 12, 16, 20 and 24

Top of page

End point title

Change From Baseline in 36-Item Short-Form Health Survey (SF-36) PCS and MCS at Week 4, 8, 12, 16, 20 and 24 ^[40]

End point description

SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as PCS and MCS. The score for each aspect and PCS/MCS is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). LOCF method was used to impute missing values. Here, 'n' =subjects evaluable at specified time point.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20, 24

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	45	47	45
Units: Units on a scale
least squares mean (confidence interval 95%)
MCS: Week 4 (n=43, 45, 45)	1.97 (-0.69 to 4.64)	1.45 (-1.14 to 4.04)	1.45 (-1.12 to 4.02)
MCS: Week 8 (n=43, 46, 45)	1.57 (-1.1 to 4.23)	1.97 (-0.59 to 4.52)	2.05 (-0.52 to 4.62)
MCS: Week 12 (n=43, 46, 45)	3.8 (1.13 to 6.46)	2.5 (-0.06 to 5.05)	2.52 (-0.05 to 5.09)
MCS: Week 16 (n=43, 46, 45)	4.73 (2.07 to 7.4)	2.79 (0.24 to 5.35)	2.95 (0.38 to 5.52)
MCS: Week 20 (n=43, 46, 45)	4.49 (1.82 to 7.15)	1.71 (-0.85 to 4.26)	3.28 (0.71 to 5.85)
MCS: Week 24 (n=43, 46, 45)	2.94 (0.28 to 5.6)	2.14 (-0.41 to 4.7)	2.85 (0.28 to 5.42)
PCS: Week 4 (n=43, 45, 45)	3.95 (1.75 to 6.15)	3.24 (1.1 to 5.38)	1.28 (-0.85 to 3.4)
PCS: Week 8 (n=43, 46, 45)	5.48 (3.27 to 7.68)	4.79 (2.68 to 6.9)	2.11 (-0.01 to 4.23)
PCS: Week 12 (n=43, 46, 45)	6.06 (3.86 to 8.26)	4.66 (2.55 to 6.77)	2.82 (0.7 to 4.95)
PCS: Week 16 (n=43, 46, 45)	6.25 (4.05 to 8.45)	4.5 (2.39 to 6.61)	2.48 (0.36 to 4.6)
PCS: Week 20 (n=43, 46, 45)	6.39 (4.19 to 8.59)	5.63 (3.52 to 7.74)	3.29 (1.17 to 5.42)
PCS: Week 24 (n=43, 46, 45)	5.98 (3.77 to 8.18)	5.53 (3.42 to 7.64)	2.94 (0.82 to 5.06)

MCS Analysis Week 4: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

0.53

Confidence interval

level

90%

sides

2-sided

lower limit

-2.53

upper limit

3.59

MCS Analysis Week 8: PF-04236921 10 mg vs Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

-0.48

Confidence interval

level

90%

sides

2-sided

lower limit

-3.54

upper limit

2.58

MCS Analysis Week 16: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

1.78

Confidence interval

level

90%

sides

2-sided

lower limit

-1.28

upper limit

4.84

MCS Analysis Week 12:PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

1.28

Confidence interval

level

90%

sides

2-sided

lower limit

-1.78

upper limit

4.34

MCS Analysis Week 20: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

1.2

Confidence interval

level

90%

sides

2-sided

lower limit

-1.86

upper limit

4.26

MCS Analysis Week 24: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

0.09

Confidence interval

level

90%

sides

2-sided

lower limit

-2.98

upper limit

3.15

MCS Analysis Week 4: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

Confidence interval

level

90%

sides

2-sided

lower limit

-3.03

upper limit

3.03

MCS Analysis Week 8: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

-0.09

Confidence interval

level

90%

sides

2-sided

lower limit

-3.09

upper limit

2.92

MCS Analysis Week 12: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

-0.02

Confidence interval

level

90%

sides

2-sided

lower limit

-3.03

upper limit

2.99

MCS Analysis Week 16: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

-0.16

Confidence interval

level

90%

sides

2-sided

lower limit

-3.17

upper limit

2.85

MCS Analysis Week 20: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

-1.58

Confidence interval

level

90%

sides

2-sided

lower limit

-4.58

upper limit

1.43

MCS Analysis Week 24: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

-0.71

Confidence interval

level

90%

sides

2-sided

lower limit

-3.72

upper limit

2.3

PCS Analysis Week 4: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

2.67

Confidence interval

level

90%

sides

2-sided

lower limit

0.14

upper limit

5.2

PCS Analysis Week 8: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

3.36

Confidence interval

level

90%

sides

2-sided

lower limit

0.84

upper limit

5.89

PCS Analysis Week 12: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

3.23

Confidence interval

level

90%

sides

2-sided

lower limit

0.7

upper limit

5.76

PCS Analysis Week 16: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

3.77

Confidence interval

level

90%

sides

2-sided

lower limit

1.24

upper limit

6.3

PCS Analysis Week 20: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

3.1

Confidence interval

level

90%

sides

2-sided

lower limit

0.57

upper limit

5.63

PCS Analysis Week 24: PF-04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

3.03

Confidence interval

level

90%

sides

2-sided

lower limit

0.5

upper limit

5.56

PCS Analysis Week 4: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

1.96

Confidence interval

level

90%

sides

2-sided

lower limit

-0.53

upper limit

4.46

PCS Analysis Week 8: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

2.68

Confidence interval

level

90%

sides

2-sided

lower limit

0.2

upper limit

5.17

PCS Analysis Week 12: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

1.84

Confidence interval

level

90%

sides

2-sided

lower limit

-0.65

upper limit

4.32

PCS Analysis Week 16: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

2.01

Confidence interval

level

90%

sides

2-sided

lower limit

-0.47

upper limit

4.5

PCS Analysis Week 20: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

2.34

Confidence interval

level

90%

sides

2-sided

lower limit

-0.15

upper limit

4.82

PCS Analysis Week 24: PF-04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

2.59

Confidence interval

level

90%

sides

2-sided

lower limit

0.11

upper limit

5.08

Secondary: Change From Baseline in Vitality Scores at Week 4, 8, 12, 16, 20 and 24

Top of page

End point title

Change From Baseline in Vitality Scores at Week 4, 8, 12, 16, 20 and 24 ^[41]

End point description

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Vitality sub-score is a component of SF-36 Health Survey Questionnaire and assesses energy and fatigue. The vitality score ranged from 0-100 (100=highest level of functioning). FAS excluding the subjects in the 200-mg dose group. LOCF method was used to impute missing values. As the SF-36 MCS component results were not significant at any timepoint, the decision was made to evaluate the vitality domain, at only Week 24 timepoint. Here, results for only Week 24 time point are reported.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20, 24

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	43	46	45
Units: Units on a scale
least squares mean (standard error)	10.3 ( 3.088 )	7.45 ( 2.983 )	6.42 ( 3.022 )

Vitality Analysis: PF04236921 10 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the treatment difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.374

Method

ANCOVA

Parameter type

Treatment Difference

Point estimate

3.87

Confidence interval

level

95%

sides

2-sided

lower limit

-4.71

upper limit

12.46

Vitality Analysis: PF04236921 50 mg v Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the treatment difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.81

Method

ANCOVA

Parameter type

Treatment Difference

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

9.46

Secondary: Change From Baseline in Short Form-6 Dimension (SF-6D) at Week 4, 8, 12, 16, 20 and 24

Top of page

End point title

Change From Baseline in Short Form-6 Dimension (SF-6D) at Week 4, 8, 12, 16, 20 and 24 ^[42]

End point description

The SF-6D focuses on seven of the eight health domains covered by the SF-36 version2(v2) Health Survey: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Only the general health domain is not included. The SF-6D index is scored from 0.0 (worst health state) to 1.0 (best health state).

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20, 24

Notes
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	0 ^[43]	0 ^[44]	0 ^[45]
Units: Units on a scale
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[43] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.
[44] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.
[45] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.

No statistical analyses for this end point

Secondary: Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Baseline

Top of page

End point title

Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Baseline ^[46]

End point description

FACIT-F is a 13-item questionnaire. Subjects scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the subject’s response to the questions (with the exception of 2 negatively stated), greater was the subject’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the subject’s response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). FAS excluding the subjects in the 200-mg dose group.

End point type

Secondary

End point timeframe

Baseline

Notes
[46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	45	47	45
Units: Units on a scale
arithmetic mean (standard deviation)	25.91 ( 1.7 )	29.38 ( 1.506 )	25.96 ( 1.76 )

No statistical analyses for this end point

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Week 4, 8, 12, 16, 20 and 24

Top of page

End point title

Change From Baseline in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Week 4, 8, 12, 16, 20 and 24 ^[47]

End point description

FACIT-F is a 13-item questionnaire. Subjects scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the subject’s response to the questions (with the exception of 2 negatively stated), greater was the subject’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the subject’s response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Here, 'n' signifies subjects evaluable for this end point at the specified time points. LOCF method was used to impute missing values.

End point type

Secondary

End point timeframe

Baseline, Week 4, 8, 12, 16, 20, 24

Notes
[47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.

End point values	PF-04236921 10 milligram (10 mg)	PF-04236921 50 mg	Placebo
Number of subjects analysed	45	47	45
Units: Units on a scale
least squares mean (confidence interval 95%)
Week 4 (n=43, 45, 45)	3.16 (0.25 to 6.07)	2.77 (-0.05 to 5.6)	1.08 (-1.72 to 3.89)
Week 8 (n=43, 46, 45)	4.39 (1.49 to 7.3)	3.41 (0.62 to 6.2)	2.44 (-0.37 to 5.24)
Week 12 (n=43, 46, 45)	5.07 (2.16 to 7.97)	3.59 (0.8 to 6.38)	2.26 (-0.54 to 5.06)
Week 16 (n=43, 46, 45)	5.81 (2.9 to 8.72)	5.53 (2.74 to 8.32)	1.93 (-0.88 to 4.73)
Week 20 (n=43, 46, 45)	5.37 (2.46 to 8.28)	4.32 (1.53 to 7.11)	3.42 (0.61 to 6.22)
Week 24 (n=43, 46, 45)	4.39 (1.49 to 7.3)	3.3 (0.51 to 6.09)	2.7 (-0.1 to 5.51)

Analysis at Week 4: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the Least Square (LS) mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

2.08

Confidence interval

level

90%

sides

2-sided

lower limit

-1.26

upper limit

5.42

Analysis at Week 8: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

1.95

Confidence interval

level

90%

sides

2-sided

lower limit

-1.38

upper limit

5.29

Analysis at Week 12: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

2.81

Confidence interval

level

90%

sides

2-sided

lower limit

-0.53

upper limit

6.15

Analysis at Week 16: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

3.88

Confidence interval

level

90%

sides

2-sided

lower limit

0.54

upper limit

7.22

Analysis at Week 20: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

1.95

Confidence interval

level

90%

sides

2-sided

lower limit

-1.39

upper limit

5.29

Analysis at Week 24: PF-04236921 10 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 10 milligram (10 mg) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

1.69

Confidence interval

level

90%

sides

2-sided

lower limit

-1.65

upper limit

5.03

Analysis at Week 4: PF-04236921 50 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

1.69

Confidence interval

level

90%

sides

2-sided

lower limit

-1.61

upper limit

4.99

Analysis at Week 8: PF-04236921 50 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

0.97

Confidence interval

level

90%

sides

2-sided

lower limit

-2.31

upper limit

4.26

Analysis at Week 12: PF-04236921 50 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

1.33

Confidence interval

level

90%

sides

2-sided

lower limit

-1.96

upper limit

4.61

Analysis at Week 16: PF-04236921 50 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

Placebo v PF-04236921 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

3.6

Confidence interval

level

90%

sides

2-sided

lower limit

0.32

upper limit

6.89

Analysis at Week 20: PF-04236921 50 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

0.91

Confidence interval

level

90%

sides

2-sided

lower limit

-2.38

upper limit

4.19

Analysis at Week 24: PF-04236921 50 mg v. Placebo

Statistical analysis description

Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.

Comparison groups

PF-04236921 50 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean difference

Point estimate

0.6

Confidence interval

level

90%

sides

2-sided

lower limit

-2.68

upper limit

3.88

Adverse events

Top of page

Timeframe for reporting adverse events

AEs/SAEs were collected from baseline up to Week 52

Adverse event reporting additional description

An AE may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. SAEs consist of all the SAEs including infectious SAEs; non-SAEs consist of all the non-SAEs including infectious non-SAEs.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

PF-04236921 10 mg

Reporting group description

Subjects received 10 mg dose of PF-04236921 subcutaneously in the anterolateral right and left thighs at Week 0, Week 8 and Week 16.

Reporting group title

PF-04236921 50 mg

Reporting group description

Subjects received 50 mg dose of PF-04236921 subcutaneously in the anterolateral right and left thighs at Week 0, Week 8 and Week 16.

Reporting group title

PF-04236921 200 mg

Reporting group description

Subjects received 200 mg dose of PF-04236921 subcutaneously in the anterolateral right and left thighs at Week 0, Week 8 and Week 16.

Reporting group title

Placebo

Reporting group description

Placebo matching to PF-04236921 administered subcutaneously in the anterolateral right and left thighs at Week 0, Week 8 and Week 16.

Serious adverse events	PF-04236921 10 mg	PF-04236921 50 mg	PF-04236921 200 mg	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 45 (8.89%)	3 / 47 (6.38%)	7 / 46 (15.22%)	8 / 45 (17.78%)
number of deaths (all causes)	1	0	3	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Aortic stenosis
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Surgical and medical procedures
Knee arthroplasty
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Endometrial hyperplasia
subjects affected / exposed	0 / 45 (0.00%)	1 / 47 (2.13%)	0 / 46 (0.00%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metrorrhagia
subjects affected / exposed	1 / 45 (2.22%)	0 / 47 (0.00%)	0 / 46 (0.00%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cyst
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian haemorrhage
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 45 (2.22%)	0 / 47 (0.00%)	2 / 46 (4.35%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 2	0 / 0
Investigations
Arthroscopy
subjects affected / exposed	1 / 45 (2.22%)	0 / 47 (0.00%)	0 / 46 (0.00%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardio
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Myocardial ischaemia
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Nervous system disorders
Headache
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vasculitis cerebral
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Visual impairment
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 45 (0.00%)	1 / 47 (2.13%)	0 / 46 (0.00%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Umbilical hernia, obstructive
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Systemic lupus erythematosus
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	2 / 45 (4.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Acute sinusitis
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 45 (0.00%)	1 / 47 (2.13%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Disseminated tuberculosis
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
Infectious mononucleosis
subjects affected / exposed	1 / 45 (2.22%)	0 / 47 (0.00%)	0 / 46 (0.00%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Latent tuberculosis
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Localised infection
subjects affected / exposed	1 / 45 (2.22%)	0 / 47 (0.00%)	0 / 46 (0.00%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis chronic
subjects affected / exposed	0 / 45 (0.00%)	1 / 47 (2.13%)	0 / 46 (0.00%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 45 (0.00%)	1 / 47 (2.13%)	1 / 46 (2.17%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	PF-04236921 10 mg	PF-04236921 50 mg	PF-04236921 200 mg	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	20 / 45 (44.44%)	24 / 47 (51.06%)	32 / 46 (69.57%)	26 / 45 (57.78%)
Vascular disorders
Hypertension
subjects affected / exposed	4 / 45 (8.89%)	2 / 47 (4.26%)	4 / 46 (8.70%)	1 / 45 (2.22%)
occurrences all number	4	2	4	1
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	0 / 45 (0.00%)	3 / 47 (6.38%)	2 / 46 (4.35%)	1 / 45 (2.22%)
occurrences all number	0	3	2	1
Pyrexia
subjects affected / exposed	0 / 45 (0.00%)	2 / 47 (4.26%)	0 / 46 (0.00%)	3 / 45 (6.67%)
occurrences all number	0	2	0	3
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 45 (2.22%)	1 / 47 (2.13%)	1 / 46 (2.17%)	3 / 45 (6.67%)
occurrences all number	1	1	1	3
Oropharyngeal pain
subjects affected / exposed	1 / 45 (2.22%)	1 / 47 (2.13%)	4 / 46 (8.70%)	2 / 45 (4.44%)
occurrences all number	1	1	4	2
Cough
subjects affected / exposed	4 / 45 (8.89%)	1 / 47 (2.13%)	1 / 46 (2.17%)	3 / 45 (6.67%)
occurrences all number	4	1	1	3
Psychiatric disorders
Insomnia
subjects affected / exposed	1 / 45 (2.22%)	1 / 47 (2.13%)	3 / 46 (6.52%)	2 / 45 (4.44%)
occurrences all number	1	1	3	2
Investigations
Hepatic enzyme increased
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	3 / 46 (6.52%)	1 / 45 (2.22%)
occurrences all number	0	0	3	1
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	3 / 45 (6.67%)	1 / 47 (2.13%)	2 / 46 (4.35%)	0 / 45 (0.00%)
occurrences all number	3	1	2	0
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 45 (2.22%)	3 / 47 (6.38%)	2 / 46 (4.35%)	2 / 45 (4.44%)
occurrences all number	1	3	2	2
Headache
subjects affected / exposed	4 / 45 (8.89%)	8 / 47 (17.02%)	5 / 46 (10.87%)	2 / 45 (4.44%)
occurrences all number	4	8	5	2
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	3 / 46 (6.52%)	0 / 45 (0.00%)
occurrences all number	0	0	3	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 45 (4.44%)	3 / 47 (6.38%)	2 / 46 (4.35%)	1 / 45 (2.22%)
occurrences all number	2	3	2	1
Abdominal pain upper
subjects affected / exposed	3 / 45 (6.67%)	0 / 47 (0.00%)	1 / 46 (2.17%)	0 / 45 (0.00%)
occurrences all number	3	0	1	0
Diarrhoea
subjects affected / exposed	2 / 45 (4.44%)	3 / 47 (6.38%)	5 / 46 (10.87%)	5 / 45 (11.11%)
occurrences all number	2	3	5	5
Nausea
subjects affected / exposed	3 / 45 (6.67%)	4 / 47 (8.51%)	6 / 46 (13.04%)	7 / 45 (15.56%)
occurrences all number	3	4	6	7
Vomiting
subjects affected / exposed	1 / 45 (2.22%)	2 / 47 (4.26%)	2 / 46 (4.35%)	3 / 45 (6.67%)
occurrences all number	1	2	2	3
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	1 / 45 (2.22%)	1 / 47 (2.13%)	3 / 46 (6.52%)	2 / 45 (4.44%)
occurrences all number	1	1	3	2
Pruritus
subjects affected / exposed	1 / 45 (2.22%)	1 / 47 (2.13%)	0 / 46 (0.00%)	3 / 45 (6.67%)
occurrences all number	1	1	0	3
Rash
subjects affected / exposed	0 / 45 (0.00%)	2 / 47 (4.26%)	4 / 46 (8.70%)	1 / 45 (2.22%)
occurrences all number	0	2	4	1
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 45 (0.00%)	3 / 47 (6.38%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	3	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 45 (2.22%)	4 / 47 (8.51%)	3 / 46 (6.52%)	4 / 45 (8.89%)
occurrences all number	1	4	3	4
Back pain
subjects affected / exposed	1 / 45 (2.22%)	3 / 47 (6.38%)	3 / 46 (6.52%)	0 / 45 (0.00%)
occurrences all number	1	3	3	0
Flank pain
subjects affected / exposed	0 / 45 (0.00%)	3 / 47 (6.38%)	0 / 46 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	3	0	1
Pain in extremity
subjects affected / exposed	0 / 45 (0.00%)	1 / 47 (2.13%)	4 / 46 (8.70%)	2 / 45 (4.44%)
occurrences all number	0	1	4	2
Systemic lupus erythematosus
subjects affected / exposed	3 / 45 (6.67%)	5 / 47 (10.64%)	2 / 46 (4.35%)	1 / 45 (2.22%)
occurrences all number	3	5	2	1
Infections and infestations
Bronchitis
subjects affected / exposed	5 / 45 (11.11%)	6 / 47 (12.77%)	3 / 46 (6.52%)	3 / 45 (6.67%)
occurrences all number	5	7	4	3
Gastroenteritis
subjects affected / exposed	1 / 45 (2.22%)	3 / 47 (6.38%)	2 / 46 (4.35%)	3 / 45 (6.67%)
occurrences all number	1	3	5	3
Pharyngitis
subjects affected / exposed	2 / 45 (4.44%)	3 / 47 (6.38%)	2 / 46 (4.35%)	4 / 45 (8.89%)
occurrences all number	2	3	2	6
Sinusitis
subjects affected / exposed	1 / 45 (2.22%)	3 / 47 (6.38%)	4 / 46 (8.70%)	0 / 45 (0.00%)
occurrences all number	1	3	5	0
Upper respiratory tract infection
subjects affected / exposed	5 / 45 (11.11%)	6 / 47 (12.77%)	11 / 46 (23.91%)	7 / 45 (15.56%)
occurrences all number	8	6	13	8
Urinary tract infection
subjects affected / exposed	8 / 45 (17.78%)	5 / 47 (10.64%)	3 / 46 (6.52%)	7 / 45 (15.56%)
occurrences all number	8	9	3	15
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	1 / 45 (2.22%)	4 / 47 (8.51%)	1 / 46 (2.17%)	1 / 45 (2.22%)
occurrences all number	1	4	1	1
Hyperglycaemia
subjects affected / exposed	3 / 45 (6.67%)	0 / 47 (0.00%)	2 / 46 (4.35%)	0 / 45 (0.00%)
occurrences all number	3	0	2	0
Hypertriglyceridaemia
subjects affected / exposed	1 / 45 (2.22%)	3 / 47 (6.38%)	3 / 46 (6.52%)	2 / 45 (4.44%)
occurrences all number	1	3	3	2
Hypoglycaemia
subjects affected / exposed	0 / 45 (0.00%)	0 / 47 (0.00%)	0 / 46 (0.00%)	3 / 45 (6.67%)
occurrences all number	0	0	0	3

More information

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Were there any global substantial amendments to the protocol? Yes

01 Jul 2011

1. Changed primary endpoint of subjects achieving SLE responder Index from Week 20 or 24 to Week 24 only. 2. Combined BILAG, SLEDAI-2K and Physician’s Global Assessment endpoints into a single endpoint of components and disposition of SRI. Added corticosteroid taper endpoint. Added endpoint for normalized serologic activity Endpoints. Clarified mean change in patient global VAS, EQ-5D, SF-36 PCS, MCS and Vitality Score –all domains over time including SF-6D, FACIT. 3. AE assessment section was modified to include the monitoring of hypersensitivity reactions to the investigational product.

01 Mar 2013

1. Due to new safety data, tuberculosis (TB) testing was added at week 12, 24, 36 and week 52 throughout the study. 2. New safety language regarding neutrophil monitoring and monitoring of tuberculosis was added. Subjects were re-evaluated at frequent intervals to monitor the absolute neutrophil counts (ANC) and for signs or symptoms of infections. If the ANC counts increased to >=750 cells per cubic millimeter (cells/mm^3) within 15 days of the next dose at either Week 8 or Week 16, the subject was discontinued and entered the follow up period. Subjects were also discontinued if they developed any symptoms or signs of febrile neutropenia during this period. Following follow up measures were added to this protocol to ensure the continued safety of subjects and to further mitigate the risk of TB infection: a) Serial TB testing (Purified Protein Derivative [PPD] or quantiferon test [QFT]) was implemented to monitor for new cases of TB during the course of study. b) Subjects were carefully monitored throughout study for signs, symptoms of TB such as chest pain, difficulty breathing, wheezing, fever, coughing up mucus or blood, excessive sweating(especially at night), lymphadenopathy, new fatigue, or new unplanned weight loss. c) If a subject converted from a negative to positive TB test during trial by serial testing, they were thoroughly evaluated to exclude TB. d) If it was confirmed that a subject had developed latent or active TB in the study based upon above evaluations, the subject received further doses of test article, and was treated standard antimycobacterial therapy. e) If treatment with steroids was required to treat a documented lupus flare, or intercurrent medical condition, a thorough evaluation was performed to exclude TB infection prior to initiating steroid therapy.

30 Apr 2013

Further dosing in the 200 mg treatment arm was stopped due to safety reasons and excluded from the primary analysis.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-04236921 IN SUBJECTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24

Primary: Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24

Secondary: Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, and 20

Secondary: Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, and 20

Secondary: Percentage of Subjects Achieving Modified Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, 20, and 24

Secondary: Percentage of Subjects Achieving Modified Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, 20, and 24

Secondary: Percentage of Subjects Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response at Week 4, 8, 12, 16, 20, and 24

Secondary: Percentage of Subjects Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response at Week 4, 8, 12, 16, 20, and 24

Secondary: Percentage of Subjects Achieving Pre-defined Criteria for Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Components at Week 24

Secondary: Percentage of Subjects Achieving Pre-defined Criteria for Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Components at Week 24

Secondary: Number of Subjects With Clinically Significant Laboratory Tests Results

Secondary: Number of Subjects With Clinically Significant Laboratory Tests Results

Secondary: Number of Subjects who Discontinued due to Adverse Events

Secondary: Number of Subjects who Discontinued due to Adverse Events

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

Secondary: Number of Subjects With Treatment-Emergent Infectious Adverse Events (AEs) or Serious Adverse Events (SAEs)

Secondary: Number of Subjects With Treatment-Emergent Infectious Adverse Events (AEs) or Serious Adverse Events (SAEs)

Secondary: Number of Subjects With Potentially Clinically Important (PCI) Electrocardiogram (ECG) Findings

Secondary: Number of Subjects With Potentially Clinically Important (PCI) Electrocardiogram (ECG) Findings

Secondary: Number of Subjects With Potentially Clinically Important Vital Signs Findings

Secondary: Number of Subjects With Potentially Clinically Important Vital Signs Findings

Secondary: Number of Subjects With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (Nabs)

Secondary: Number of Subjects With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (Nabs)

Secondary: Serum concentration of PF-04236921

Secondary: Serum concentration of PF-04236921

Secondary: Percentage of Subjects With Corticosteroid Dose Reduced by Both Greater Than or Equal to (>=) 25 Percent (%) From Baseline and Less Than or Equal to (<=) 7.5 Milligrams per day (mg/day)

Secondary: Percentage of Subjects With Corticosteroid Dose Reduced by Both Greater Than or Equal to (>=) 25 Percent (%) From Baseline and Less Than or Equal to (<=) 7.5 Milligrams per day (mg/day)

Secondary: Percentage of Subjects With Normalized Serological Activity

Secondary: Percentage of Subjects With Normalized Serological Activity

Secondary: Patient Global Visual Analog Scale (VAS) Scores at Baseline

Secondary: Patient Global Visual Analog Scale (VAS) Scores at Baseline

Secondary: Change From Baseline in Patient Global Visual Analog Scale (VAS) at Week 2, 4, 6, 8, 12, 16, 20 and 24

Secondary: Change From Baseline in Patient Global Visual Analog Scale (VAS) at Week 2, 4, 6, 8, 12, 16, 20 and 24

Secondary: Change From Baseline in European Quality of Life 5 Dimensions Questionnaire (EQ-5D) at Week 4, 8, 12, 16, 20 and 24

Secondary: Change From Baseline in European Quality of Life 5 Dimensions Questionnaire (EQ-5D) at Week 4, 8, 12, 16, 20 and 24

Secondary: Thirty six-Item Short-Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Baseline

Secondary: Thirty six-Item Short-Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Baseline

Secondary: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) PCS and MCS at Week 4, 8, 12, 16, 20 and 24

Secondary: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) PCS and MCS at Week 4, 8, 12, 16, 20 and 24

Secondary: Change From Baseline in Vitality Scores at Week 4, 8, 12, 16, 20 and 24

Secondary: Change From Baseline in Vitality Scores at Week 4, 8, 12, 16, 20 and 24

Secondary: Change From Baseline in Short Form-6 Dimension (SF-6D) at Week 4, 8, 12, 16, 20 and 24

Secondary: Change From Baseline in Short Form-6 Dimension (SF-6D) at Week 4, 8, 12, 16, 20 and 24

Secondary: Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Baseline

Secondary: Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Baseline

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Week 4, 8, 12, 16, 20 and 24

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Week 4, 8, 12, 16, 20 and 24

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-04236921 IN SUBJECTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)